非糖尿病患者肾小管健康的尿液生物标志物与慢性肾脏病发病风险：动脉粥样硬化风险社区研究（ARIC）、多族裔动脉粥样硬化研究（MESA）及地理和种族多样化队列研究（REGARDS）
Urine Biomarkers of Kidney Tubule Health and Risk of Incident CKD in Persons Without Diabetes: The ARIC, MESA, and REGARDS Studies.
作者信息
Amatruda Jonathan G, Katz Ronit, Rebholz Casey M, Sarnak Mark J, Gutierrez Orlando M, Schrauben Sarah J, Greenberg Jason H, Coresh Josef, Cushman Mary, Waikar Sushrut, Parikh Chirag R, Schelling Jeffrey R, Jogalekar Manasi P, Bonventre Joseph V, Vasan Ramachandran S, Kimmel Paul L, Ix Joachim H, Shlipak Michael G
机构信息
Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA.
Kidney Health Research Collaborative, San Francisco VA Medical Center & University of California, San Francisco, San Francisco, CA.
出版信息
Kidney Med. 2024 Apr 26;6(6):100834. doi: 10.1016/j.xkme.2024.100834. eCollection 2024 Jun.
RATIONALE & OBJECTIVE: Tubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD.
STUDY DESIGN
Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]).
SETTING & PARTICIPANTS: Adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m and without diabetes in the ARIC, REGARDS, and MESA studies.
EXPOSURES
Baseline urine monocyte chemoattractant protein-1 (MCP-1), alpha-1-microglobulin (α1m), kidney injury molecule-1, epidermal growth factor, and chitinase-3-like protein 1.
OUTCOME
Incident CKD or end-stage kidney disease.
ANALYTICAL APPROACH
Multivariable Cox proportional hazards regression for each cohort; meta-analysis of results from all 3 cohorts.
RESULTS
872 ARIC participants (444 cases of incident CKD), 636 MESA participants (158 cases), and 924 REGARDS participants (488 cases) were sampled. Across cohorts, mean age ranged from 60 ± 10 to 63 ± 8 years, and baseline eGFR ranged from 88 ± 13 to 91 ± 14 mL/min/1.73 m. In ARIC, higher concentrations of urine MCP-1, α1m, and kidney injury molecule-1 were associated with incident CKD. In MESA, higher concentration of urine MCP-1 and lower concentration of epidermal growth factor were each associated with incident CKD. In REGARDS, none of the biomarkers were associated with incident CKD. In meta-analysis of all 3 cohorts, each 2-fold increase α1m concentration was associated with incident CKD (HR, 1.19; 95% CI, 1.08-1.31).
LIMITATIONS
Observational design susceptible to confounding; competing risks during long follow-up period; meta-analysis limited to 3 cohorts.
CONCLUSIONS
In 3 combined cohorts of adults without prevalent CKD or diabetes, higher urine α1m concentration was independently associated with incident CKD. 4 biomarkers were associated with incident CKD in at least 1 of the cohorts when analyzed individually. Kidney tubule health markers might inform CKD risk independent of eGFR and albuminuria.
原理与目的
肾小管间质损伤是早期慢性肾脏病（CKD）的一个特征，但目前的临床检测对其捕捉效果不佳。肾小管间质健康的尿液生物标志物可能有助于识别CKD风险。
研究设计
前瞻性队列研究（社区动脉粥样硬化风险研究[ARIC]）以及病例队列研究（动脉粥样硬化多族裔研究[MESA]和中风地理与种族差异原因研究[REGARDS]）。
设置与参与者
ARIC、REGARDS和MESA研究中估算肾小球滤过率（eGFR）≥60 mL/min/1.73 m²且无糖尿病的成年人。
暴露因素
基线尿液单核细胞趋化蛋白-1（MCP-1）、α1-微球蛋白（α1m）、肾损伤分子-1、表皮生长因子和几丁质酶-3样蛋白1。
结局
新发CKD或终末期肾病。
分析方法
对每个队列进行多变量Cox比例风险回归分析；对所有3个队列的结果进行荟萃分析。
结果
对872名ARIC参与者（444例新发CKD病例）、636名MESA参与者（158例）和924名REGARDS参与者（488例）进行了抽样。各队列中，平均年龄在60±10岁至63±8岁之间，基线eGFR在88±13 mL/min/1.73 m²至91±14 mL/min/1.73 m²之间。在ARIC中，尿液MCP-1、α1m和肾损伤分子-1浓度较高与新发CKD相关。在MESA中，尿液MCP-1浓度较高和表皮生长因子浓度较低均与新发CKD相关。在REGARDS中，没有生物标志物与新发CKD相关。在对所有3个队列的荟萃分析中，α1m浓度每增加2倍与新发CKD相关（风险比[HR]，1.19；95%置信区间[CI]，1.08 - 1.31）。
局限性
观察性设计易受混杂因素影响；长期随访期间存在竞争风险；荟萃分析仅限于3个队列。
结论
在3个合并队列的无CKD或糖尿病病史的成年人中，尿液α1m浓度较高与新发CKD独立相关。单独分析时，4种生物标志物在至少1个队列中与新发CKD相关。肾小管健康标志物可能有助于独立于eGFR和蛋白尿来判断CKD风险。
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